Triethylamine → (3R)-3-[3-({[1-(tert-butoxycarbonyl)-3-azetidinyl]amino}carbonyl)-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoic acid

HRID 1279868Notes

Reaction equation

HRID 1279868 reaction equation
[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([O:22]CC)=O)[N:16]=2)[CH2:11][C:12]([OH:14])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[NH2:32][CH:33]1[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:34]1>C(O)C>[C:40]([O:39][C:37]([N:35]1[CH2:36][CH:33]([NH:32][C:20]([C:17]2[N:16]=[C:15]([C@H:10]([CH2:9][CH2:8][CH2:7][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[CH2:11][C:12]([OH:14])=[O:13])[O:19][N:18]=2)=[O:22])[CH2:34]1)=[O:38])([CH3:43])([CH3:41])[CH3:42]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1516507Tert-butyl 3-aminoazetidine-1-carboxylateHCID 59909750(3R)-6-cyclohexyl-3-[3-(ethoxycarbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid

Product 1

HCID 59909788(3R)-3-[3-({[1-(tert-butoxycarbonyl)-3-azetidinyl]amino}carbonyl)-1,2,4-oxadiazol-5-yl]-6-cyclohexylhexanoic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A solution of (3R)-6-cyclohexyl-3-[3-(ethoxycarbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid (Preparation 4) (480 mg, 1.42 mmol) and triethylamine (1 ml, 7.18 mmol) in ethanol (8 ml) was treated with tert-butyl 3-amino-1-azetidinecarboxylate (Preparation 78) (300 mg, 1.74 mmol) and the resulting mixture was heated at 80° C. under a nitrogen atmosphere for 18 hours. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (99:1) gradually changing to dichloromethane:methanol (90:10) to afford the title compound contaminated with starting amine. The solid was dissolved in ethyl acetate and washed with hydrochloric acid (0.5M) (2×), water and brine, dried over magnesium sulphate, filtered and the solvent was removed under reduced pressure to afford the title compound as a sticky foam.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (99:1)

Sources & evidence

ORD record
ord-7ea874dc81fc481a9bbb04bebeeb7903
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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